文献类型：期刊文献

中文题名：杂交瘤细胞流加培养过程中不同拟稳态下的代谢动力学分析

英文题名：Metabolism Dynamic Analysis of Hybridoma Cells at Distinct Fed-Batch Culture Pseudo-steady States

作者：牛红星[1];朱明龙[1];谭文松[1]

机构：[1]华东理工大学生物反应器工程国家重点实验室,上海200237

年份：2007

卷号：33

期号：6

起止页码：774

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：CSTPCD;;EI(收录号：20080411059278);Scopus;北大核心:【北大核心2004】；CSCD:【CSCD2011_2012】；

基金：国家863项目(2004AA2Z3794)

语种：中文

中文关键词：流加培养;代谢动力学;杂交瘤细胞;拟稳态

外文关键词：fed batch culture; metabolism dynamics; hybridoma cells; pseudo-steady state

摘要：采用流加培养方式，实现了杂交瘤细胞在营养物富裕、葡萄糖限制和谷氨酰胺限制3种条件下的拟稳态培养。代谢动力学分析表明：葡萄糖限制时，葡萄糖比消耗速率（qGluc）降低到1.1×10^-9mmol/（cell·d），相比营养物富裕时降低了40％以上；乳酸生成量降到最低。谷氨酰胺限制时，谷氨酰胺的最小比消耗速率（qGln）约为0.28×10^-9mmol/（cell·d），相比营养物富裕时降低了56％以上；氨的比生成速率降低到0.23×10^-9mmol/（cell·d），营养物富裕时为0.93×10^-9mmol/（cell·d）；丙氨酸的生成降到最低。3种拟稳态下单抗的比生成速率都在29×10^-9～37×10^-9mg/（cell·d）。本文的流加培养设计方法为快速认识细胞的代谢规律，设计相应的培养基和调控策略，实现细胞高密度和产物高浓度的培养过程提供了指导。
With rational design of fed-batch culture processes, hybridoma cells were grown under nutrient-fortified, glucose limited and glutamine limited conditions to typical pseudo-steady states, respectively. Dynamic metabolic analysis found that, the specific consumption rate of glucose （qGluc） was reduced to 1.1×10^-9mmol/（cell·d） under the glucose limited condition, 40% lower than that under nutrient-fortified condition, and lactate formation was decreased to minimal value. On the other hand, the specific consumption rate of glutamine （qGln） was reduced to 0.28×10^-9mmol/（cell·d） under the glutamine-limited condition, 56% lower than that under nutrient-fortified condition, and the specific formation rate of ammonia was reduced from 0.93×10^-9mmol/（cell·d） under nutrient-fortified condition to 0.23×10^-9mmol/（cell·d） with minimal alanine formation. It was found that the specific production rate of antibody remained basically unchanged under these altered conditions. The fed batch processes design methods adopted will provide a valuable guidance for the understanding of cells metabolism mechanism rapidly aiming for the rational design of cell culture media and metabolism manipulation during bioreactor operation to achieve productive processes with both high cell density and high product yield.